Biomedical subjects

D Contreras

Publications and source records attributed to D Contreras.

At least 37 records · Page 2Linked to original sources

PubMed1997

Spindle oscillations during cortical spreading depression in naturally sleeping cats.

Spindling activity characterizes the EEG of animals and humans in the early stages of resting sleep. Spindles are defined as waxing and waning rhythmic waves at 7-14 Hz that recur periodically every 3-10 s. Spindling originates in the thalamus, but a role for the cerebral cortex in triggering and synchronizing thalamic spindles was shown by stimulation of the contralateral cortex avoiding antidromic activation of thalamocortical axons and by diminished coherency of thalamic spindles after hemidecortication. Spontaneous spindles under barbiturate anesthesia are waxing and waning but under ketamine-xylazine anesthesia or when evoked by strong stimuli spindle waves are almost exclusively waning, i.e. they start with maximum amplitude and then decrease progressively. Waxing and waning of spindles has been ascribed to progressive entrainment of units into the oscillation followed by a progressive desynchronization. Therefore, exclusively waning spindles would be produced by an initial high synchrony in the corticothalamic network. Such a situation is observable upon strong stimulation or, spontaneously, when spindles are paced by the slow cortical oscillation and preceded by a strong corticothalamic drive. We have conducted experiments in naturally sleeping cats to verify the occurrence of two patterns of spindle oscillations and to test the role of the cortex in synchronizing and shaping spindles. We have found that indeed two types of spindles (waxing and waning or mostly waning) occur in naturally sleeping animals. We also demonstrate that during cortical spreading depression spindles are less synchronous and only of the waxing and waning type. As cortical activity recovers, waning spindles reappear and are preceded by electroencephalogram deflections which are related to corticothalamic depolarizing inputs. Our results strongly support the hypothesis of the role of the cerebral cortex in shaping and synchronizing thalamically generated spindles.

Animals↗

PubMed1997

Plateau potentials in cat neocortical association cells in vivo: synaptic control of dendritic excitability.

The dendrites of neocortical pyramidal cells are bombarded by myriads of synaptic inputs and express active conductances generating prominent plateau potentials. We have examined in vivo the possibility that spontaneous synaptic inputs trigger or terminate plateau potentials after blockage of K+ currents. Under barbiturate anaesthesia, pairs of cortical cells were intracellularly recorded with sharp electrodes from the cat's association cortex (areas 5-7). In one pyramidal cell, K+ channels were blocked with intracellular Cs+, while in the simultaneously impaled pyramidal cell the K+ conductances were left intact to act as a control; this second cell allowed recognition of spontaneous spindle-related synaptic activity. Depolarizing current pulses elicited single, all-or-none plateau potentials (60-70 mV, 0.1-0.4 s). Plateau potentials slowly repolarized towards a break point of fast repolarization around -20 mV. Thalamic-evoked inhibitory postsynaptic potentials consistently shut off the plateaus. Synchronized spontaneous activity, as occurring during thalamic-generated spindle oscillations, either triggered or blocked the plateaus. These results suggest that spontaneously occurring synaptic activation during synchronized oscillatory states, such as those that occur during sleep spindles in vivo, may exert a strong control over the dendritic excitability in neocortical pyramidal cells.

Action Potentials↗

PubMed1997

Dynamic interactions determine partial thalamic quiescence in a computer network model of spike-and-wave seizures.

In vivo intracellular recording from cat thalamus and cortex was performed during spontaneous spike-wave seizures characterized by synchronously firing cortical neurons correlated with the electroencephalogram. During these seizures, thalamic reticular (RE) neurons discharged with long spike bursts riding on a depolarization, whereas thalamocortical (TC) neurons were either entrained into the seizures (40%) or were quiescent (60%). During quiescence, TC neurons showed phasic inhibitory postsynaptic potentials (IPSPs) that coincided with paroxysmal depolarizing shifts in the simultaneously recorded cortical neuron. Computer simulations of a reciprocally connected TC-RE pair showed two major modes of TC-RE interaction. In one mode, a mutual oscillation involved direct TC neuron excitation of the RE neuron leading to a burst that fed back an IPSP into the TC neuron, producing a low-threshold spike. In the other, quiescent mode, the TC neuron was subject to stronger coalescing IPSPs. Simulated cortical stimulation could trigger a transition between the two modes. This transition could go in either direction and was dependent on the precise timing of the input. The transition did not always follow the stimulation immediately. A larger, multicolumnar simulation was set up to assess the role of the TC-RE pair in the context of extensive divergence and convergence. The amount of TC neuron spiking generally correlated with the strength of total inhibitory input, but large variations in the amount of spiking could be seen. Evidence for mutual oscillation could be demonstrated by comparing TC neuron firing with that in reciprocally connected RE neurons. An additional mechanism for TC neuron quiescence was assessed with the use of a cooperative model of gamma-aminobutyric acid-B (GABA(B))-mediated responses. With this model, RE neurons receiving repeated strong excitatory input produced TC neuron quiescence due to burst-duration-associated augmentation of GABA(B) current. We predict the existence of spatial inhomogeneity in apparently generalized spike-wave seizures, involving a center-surround pattern. In the center, intense cortical and RE neuron activity would be associated with TC neuron quiescence. In the surround, less intense hyperpolarization of TC neurons would allow low-threshold spikes to occur. This surround, an "epileptic penumbra," would be the forefront of the expanding epileptic wave during the process of initial seizure generalization. Therapeutically, we would then predict that agents that reduce TC neuron activity would have a greater effect on seizure onset than on ongoing spike-wave seizures or other thalamic oscillations.

Action Potentials↗

PubMed1997

Intracellular and computational characterization of the intracortical inhibitory control of synchronized thalamic inputs in vivo.

We investigated the presence and role of local inhibitory cortical control over synchronized thalamic inputs during spindle oscillations (7-14 Hz) by combining intracellular recordings of pyramidal cells in barbiturate-anesthetized cats and computational models. The recordings showed that 1) similar excitatory postsynaptic potential (EPSP)/inhibitory postsynaptic potential (IPSP) sequences occurred either during spindles or following thalamic stimulation; 2) reversed IPSPs with chloride-filled pipettes transformed spindle-related EPSP/IPSP sequences into robust bursts with spike inactivation, resembling paroxysmal depolarizing shifts during seizures; and 3) dual simultaneous impalements showed that inhibition associated with synchronized thalamic inputs is local. Computational models were based on reconstructed pyramidal cells constrained by recordings from the same cells. These models showed that the transformation of EPSP/IPSP sequences into fully developed spike bursts critically needs a relatively high density of inhibitory currents in the soma and proximal dendrites. In addition, models predict significant Ca2+ transients in dendrites due to synchronized thalamic inputs. We conclude that synchronized thalamic inputs are subject to strong inhibitory control within the cortex and propose that 1) local impairment of inhibition contributes to the transformation of spindles into spike-wave-type discharges, and 2) spindle-related inputs trigger Ca2+ events in cortical dendrites that may subserve plasticity phenomena during sleep.

Animals↗

PubMed1997

Absence of a prevalent laminar distribution of IPSPs in association cortical neurons of cat.

Absence of a prevalent laminar distribution of IPSPs in association cortical neurons of cat. J. Neurophysiol. 78: 2742-2753, 1997. The depth distribution of inhibitory postsynaptic potentials (IPSPs) was studied in cat suprasylvian (association) cortex in vivo. Single and dual simultaneous intracellular recordings from cortical neurons were performed in the anterior part of suprasylvian gyrus (area 5). Synaptic responses were obtained by stimulating the suprasylvian cortex, 2-3 mm anterior to the recording site, as well as the thalamic lateral posterior (LP) nucleus. Neurons were recorded from layers 2 to 6 and were classified as regular spiking (RS, n = 132), intrinsically bursting (IB, n = 24), and fast spiking (FS, n = 4). Most IB cells were located in deep layers (below 0.7 mm, n = 19), but we also found some IB cells more superficially (between 0.2 and 0.5 mm, n = 5). Deeply lying corticothalamic neurons were identified by their antidromic invasion on thalamic stimulation. Neurons responded with a combination of excitatory postsynaptic potentials (EPSPs) and IPSPs to both cortical and thalamic stimulation. No consistent relation was found between cell type or cell depth and the amplitude or duration of the IPSPs. In response to thalamic stimulation, RS cells had IPSPs of 7.9 +/- 0.9 (SE) mV amplitude and 88.9 +/- 6.4 ms duration. In IB cells, IPSPs elicited by thalamic stimulation had 7.4 +/- 1.3 mV amplitude and 84.7 +/- 14.3 ms duration. The differences between the two (RS and IB) groups were not statistically significant. Compared with thalamically elicited inhibitory responses, cortical stimulation evoked IPSPs with higher amplitude (12.3 +/- 1.7 mV) and longer duration (117 +/- 17.3 ms) at all depths. Both cortically and thalamically evoked IPSPs were predominantly monophasic. Injections of Cl- fully reversed thalamically as well as cortically evoked IPSPs and revealed additional late synaptic components in response to cortical stimulation. These data show that the amount of feed forward and feedback inhibition to cat's cortical association cells is not orderly distributed to distinct layers. Thus local cortical microcircuitry goes beyond the simplified structure determined by cortical layers.

Animals↗

PubMed1996

Control of spatiotemporal coherence of a thalamic oscillation by corticothalamic feedback.

The mammalian thalamus is the gateway to the cortex for most sensory modalities. Nearly all thalamic nuclei also receive massive feedback projections from the cortical region to which they project. In this study, the spatiotemporal properties of synchronized thalamic spindle oscillations (7 to 14 hertz) were investigated in barbiturate-anesthetized cats, before and after removal of the cortex. After complete ipsilateral decortication, the long-range synchronization of thalamic spindles in the intact cortex hemisphere changed into disorganized patterns with low spatiotemporal coherence. Local thalamic synchrony was still present, as demonstrated by dual intracellular recordings from nearby neurons. In the cortex, synchrony was insensitive to the disruption of horizontal intracortical connections. These results indicate that the global coherence of thalamic oscillations is determined by corticothalamic projections.

Anesthesia↗

PubMed1996

Mechanisms of long-lasting hyperpolarizations underlying slow sleep oscillations in cat corticothalamic networks.

1. To explore the nature of the long-lasting hyperpolarizations that characterize slow oscillations in corticothalamic circuits in vivo, intracellular recordings were obtained under ketamine-xylazine anaesthesia from cortical (Cx) cells of the cat precruciate motor cortex, thalamic reticular (RE) cells from the rostrolateral sector, and thalamocortical (TC) cells from the ventrolateral (VL) nucleus. 2. Measurements in the three cell types showed input resistance (Rin) to be highest during the long-lasting hyperpolarizations that correspond to depth-positive waves of the cortical EEG. Rin was lowest during the early phase of high-amplitude depth-negative EEG waves and increased thereafter until the next cycle of the slow oscillation. 3. Spontaneous long-lasting hyperpolarizations were compared with those evoked by dorsal thalamic stimulation. Voltage versus current (V-I) plots showed similar membrane potential (Vm) ranges and slopes for spontaneous and evoked hyperpolarizations in both Cx and RE cells. V-I plots from TC cells had similar slopes, but Vm during evoked hyperpolarizations was displaced towards more negative values. 4. Intracellular injection of constant hyperpolarizing current in Cx cells increased the amplitude of the initial part of the depolarizing plateau of the slow oscillation, but decreased the amplitude of the last part. 5. These results suggest disfacilitation to be the dominant mechanism in the membrane of cortical and thalamic cells during the spontaneous long-lasting hyperpolarizations, which shape and synchronize slow oscillations in corticothalamic networks. In Cx and RE cells, the same mechanism underlies thalamically evoked long-lasting hyperpolarizations. By contrast, evoked responses in TC cells show a strong additional hyperpolarizing factor. We propose that GABAB processes are stronger in TC than in Cx neurones, thus rendering the thalamus an easier target for absence-type epileptic phenomena through potentiation of thalamic rebound capabilities.

Animals↗

PubMed1996

Synaptic responsiveness of cortical and thalamic neurones during various phases of slow sleep oscillation in cat.

1. The fluctuations during various phases of the slow sleep oscillation (< 1 Hz) in synaptic responsiveness of motor cortical (Cx), thalamic reticular (RE) and thalamocortical (TC) neurones were investigated intracellularly in cats under ketamine-xylazine anaesthesia. Orthodromic responses to stimuli applied to brachium conjunctivum (BC) axons and corticothalamic pathways were studied. The phases of slow oscillation consist of a long-hyperpolarized, followed by a sharp depth-negative EEG deflection and a series of faster waves that are associated with the depolarization of Cx and RE neurones, while TC cells display a sequence of IPSPs within the spindle frequency. 2. BC-evoked bisynaptic excitatory postsynaptic potentials (EPSPs) in Cx and RE neurones were drastically reduced in amplitude during the long-lasting hyperpolarization and the early part of the depolarizing phase. By contrast, the BC-evoked monosynaptic EPSPs of TC cells were not diminished during the depth-positive EEG wave, but the hyperpolarization during this phase of the slow oscillation prevented TC neurones transferring prethalamic signals to the cortex. 3. At variance with the diminished bisynaptic EPSPs evoked in response to BC stimuli during the long-lasting hyperpolarization, Cx-evoked monosynaptic EPSPs in Cx cells increased linearly with hyperpolarization during this phase of the slow oscillation. Similarly, the amplitudes of Cx-evoked EPSPs in RE and TC cells were not diminished during the long-lasting hyperpolarization. 4. The diminished responsiveness of Cx and RE neurones to prethalamic volleys during the long-lasting hyperpolarization is attributed to gating processes at the level of TC cells that, because of their hyperpolarization, do not transfer prethalamic information to further relays.

Animals↗

PubMed1996

Synchronization of fast (30-40 Hz) spontaneous oscillations in intrathalamic and thalamocortical networks.

The synchronization of fast (mainly 30 to 40 Hz) oscillations in intrathalamic and thalamocortical (TC) networks of cat was studied under ketamine-xylazine anesthesia and in behaving animals by means of field potential, extra- and intracellular recordings from multiple sites in the thalamic reticular (RE) nucleus, dorsal (sensory, motor, and intralaminar) thalamic nuclei, and related neocortical areas. Far from being restricted to tonically activated behavioral states, the fast oscillations also appeared during resting sleep and deep anesthesia, when they occurred over the depolarizing component of the slow (<1 Hz) oscillation and were suppressed during the prolonged hyper-polarizations of RE, TC, and cortical neurons. The synchronization of fast rhythms among different thalamic foci was robust. Fast rhythmic cortical waves and subthreshold depolarizing potentials in TC neurons were highly coherent; however, the synchronization of the fast oscillation required recordings from reciprocally related neocortical and thalamic foci, as identified by monosynaptic responses in both directions. The short-range spatial confinement of coherent fast rhythms contrasted with the large-scale synchronization of low-frequency sleep rhythms. Transient fast rhythms, appearing over the depolarizing envelope of the slow sleep oscillation, became sustained when brain activation was elicited by stimulation of mesopontine cholinergic nuclei or during brain-active behavioral states in chronic experiments. These data demonstrate that fast rhythms are part of the background electrical activity of the brain and that desynchronization, used to designate brain-active states, is an erroneous term inasmuch as the fast oscillations are synchronized not only in intracortical but also in intrathalamic and TC networks.

Action Potentials↗

PubMed1996

Spindle oscillation in cats: the role of corticothalamic feedback in a thalamically generated rhythm.

1. Spindles represent an oscillatory activity (7-14 Hz) of the electroencephalogram (EEG) originating in the thalamus and appearing during early stages of sleep. We investigated: (i) the phase relations between thalamic and cortical neurons during this rhythm; (ii) the patterns of spindles under different anaesthetics and their modifications at various levels of the membrane potential (Vm); and (iii) the potentiating role of the corticothalamic feedback in the genesis of spindles. Intra- and extracellular recordings were performed in cats from reticular and dorsal thalamic nuclei, as well as from various cortical areas. 2. In thalamic reticular neurons, spindles were sequences of waves at 7-14 Hz, riding on a prolonged depolarizing plateau and occurring in phase with depth-negative cortical EEG waves. In thalamocortical cells, spindles consisted of inhibitory postsynaptic potentials (IPSPs) in phase with depth-positive cortical EEG waves and occasionally leading to rebound spike bursts. In cortical cells, spindle waves were rhythmic (7-14 Hz) excitatory postsynaptic potentials (EPSPs) that sometimes gave rise to action potentials. Spindles occurred in phase among thalamic reticular, thalamocortical and neocortical neurons. 3. In thalamic reticular neurons, spindle waves and their depolarizing plateaux increased in amplitude with slight cellular hyperpolarization, but at a Vm more negative than -80 or -85 mV they decreased in amplitude. No frequency alterations were observed with these Vm changes. 4. The waxing-and-waning pattern of spontaneous spindles under barbiturate anaesthesia was distinct from the waning pattern under ketamine-xylazine anaesthesia. Under all anaesthetics, spindles had a waning pattern when elicited by cortical stimuli. The amplitude of cortical-evoked spindle waves diminished with the decrease in stimulation intensity. 5. Under urethane or ketamine-xylazine anaesthesia, spindle sequences were grouped by a cortically generated slow oscillation (< 1 Hz) and were preceded by a depth-positive EEG wave that corresponded to a prolonged hyperpolarization in all three investigated (cortical, thalamic reticular, and thalamocortical) cellular types. 6. We propose that the waxing pattern of spindle oscillation is due to a progressive entrainment of units into the oscillation until a maximum number is reached, depending on the background activity in the network. The phase relations between cortical, thalamic reticular and thalamocortical neurons are ascribed to distributed excitatory signals from thalamocortical neurons to both cortical and reticular neurons at each cycle of the oscillation. In turn, cortical neurons provide a powerful drive to potentiate the genesis of thalamic spindles.

Animals↗

PubMed1996

In vivo, in vitro, and computational analysis of dendritic calcium currents in thalamic reticular neurons.

Thalamic reticular (RE) neurons are involved in the genesis of synchronized thalamocortical oscillations, which depend in part on their complex bursting properties. We have investigated the intrinsic properties of RE cells using computational models based on morphological and electrophysiological data. Simulations of a reconstructed RE cells were compared directly with recordings from the same cell to obtain precise values for the passive parameters. In a first series of experiments, the low-threshold calcium current (I(Ts)) was studied via voltage clamp in acutely dissociated RE cells that lack most of their dendrites. Simulations based on a cell with truncated dendrites and Hodgkin-Huxley kinetics reproduced these recordings with a relatively low density of I(Ts). In a second series of experiments, voltage-clamp recordings obtained in intact RE cells in slices showed a higher amplitude and slower kinetics of I(Ts). These properties could be reproduced from the reconstructed cell model assuming higher densities of I(Ts) in distal dendrites. In a third series of experiments, current-clamp recordings were obtained on RE cells in vivo. The marked differences with in vitro recordings could be reconciled by simulating synaptic bombardment in the dendrites of RE cells, but only if they contained high distal densities of I(Ts). In addition, simpler models with as few as three compartments could reproduce the same behavior assuming dendritic I(Ts). These models and experiments show how intrinsic bursting properties of RE cells, as recorded in vivo and in vitro, may be explained by dendritic calcium currents.

Animals↗

PubMed1996

Synchronization of fast (30-40 Hz) spontaneous cortical rhythms during brain activation.

We investigated the synchronization of fast spontaneous oscillations (mainly 30-40 Hz) in anesthetized and behaving cats by means of simultaneous extra- and intracellular recordings from multiple neocortical areas. Fast Fourier transforms, auto- and cross-correlations, and spike- or wave-triggered averages were used to determine the frequency and temporal coherence of fast oscillations that outlasted the stimulation of ascending activating systems or that occurred naturally during behavioral states of waking and rapid eye movement (REM) sleep but also appeared during the depolarizing phases of slow sleep oscillations. In 90% of microelectrode tracks, the fast oscillations did not show field reversal at any depth of the cortex and were not observable in the underlying white matter. The negative field potentials of the fast oscillations were associated at all depths with neuronal firing. This field potential property of fast oscillations was in sharp contrast to the reversal of slow sleep oscillation or evoked potentials at depths of 0.25-0.5 mm. The coherence of fast spontaneous rhythms was spatially limited, being confined within a cortical column and among closely located neocortical sites, in contrast to the long-range synchronization of slow sleep rhythms. Depolarizing current pulses elicited spike-bursts (200-400 Hz) recurring at a frequency of 30-40 Hz. Our experiments demonstrate that the conventional notion of a totally desynchronized cortical activity upon arousal should be revised as fast rhythms are enhanced and synchronized within intracortical networks during brain activation. Spontaneously occurring, subthreshold membrane potential depolarizing oscillations may bias cortical and thalamic neurons to respond synchronously, at fast frequencies, to relevant stimuli in the wake state or to internally generated drives in REM sleep.

Animals↗

PubMed1995

Cellular basis of EEG slow rhythms: a study of dynamic corticothalamic relationships.

A slow oscillation (< 1 Hz) has recently been described in intracellular recordings from the neocortex and thalamus (Steriade et al., 1993c-e). The aim of the present study was to determine the phase relations between cortical and thalamic neuronal activities during the slow EEG oscillation. Intracellular recordings were performed in anesthetized cats from neurons in motor and somatosensory cortical areas, the rostrolateral sector of the reticular (RE) thalamic nucleus, and thalamocortical (TC) cells from ventrolateral (VL) nucleus. The EEG was used as time reference for alignment of activities in different, simultaneously recorded neurons, including dual impalements of cortical cells as well as cortical and TC cells. The spontaneous EEG oscillation was characterized by slowly recurring (0.3-0.9 Hz) sequences of surface-positive (depth-negative) sharp deflections, often followed by oscillatory activity within the frequency range of sleep spindles (7-14 Hz) or at faster frequencies. Cortical and RE cells were similarly hyperpolarized during the depth-positive EEG waves and were depolarized during the depth-negative EEG deflections. In many instances, the cell depolarization was associated with oscillations at the spindle frequency or with tonic firing at rates related to the level of depolarization. TC neurons were hyperpolarized during the depth-positive EEG waves and displayed a series of IPSPs, at the spindle frequencies, during the depth-negative EEG waves. Depending on the membrane potential (Vm), TC cells could fire spike bursts at the onset of the EEG depth-negativity, or their firing could be delayed by subsequent IPSPs. The sequence of spontaneous EEG and cellular events described above also characterized the responses to cortical and thalamic stimulation. Simultaneous intracellular recordings of pairs of cortical cells or cortical and TC cells showed that spontaneous transitions from less synchronized to more synchronized EEG states were marked by a simultaneous hyperpolarization, coincident with an overt depth-positive EEG wave. We conclude that during low-frequency oscillatory states, characteristic of slow-wave sleep, neocortical and thalamic neurons display phase relations that are restricted to narrow time windows, and that synchronization results from a generalized inhibitory phenomenon. Moreover, EEG synchronization is reflected as active inhibition in TC neurons. That this pattern is also present in states of hypersynchronization, such as seizure activity, is shown in the following paper (Steriade and Contreras, 1994).

Animals↗

PubMed1995

Relations between cortical and thalamic cellular events during transition from sleep patterns to paroxysmal activity.

We investigated in anesthetized cats the progressive development from EEG-synchronized sleep patterns to low-frequency (< 15 Hz) paroxysmal activities, most of them consisting of epileptic-like seizures with spike-wave (SW) complexes at 2-4 Hz. We used multisite extra- and intracellular recordings of neocortical, reticular thalamic (RE), and thalamocortical (TC) neurons, including dual impalements of cortical and TC cells. A subsample (40%) of TC cells discharged spike bursts at 2-4 Hz, in close time relation with the spiky, depth-negative field components of SW seizures in related neocortical areas. Full synchronization among TC cells that were resonant with the cortical seizure activity was progressively reached toward the end of the SW paroxysm. The remaining TC cells (60%) were inhibited during the cortical SW seizures. We show that the duration and amplitude of hyperpolarization in TC cells paralleled the extent of cortical EEG paroxysm. Dual intracellular recordings of cortical and TC neurons demonstrate that during the cortical SW seizure, consisting of a tonic depolarization with superimposed paroxysmal spike bursts, the simultaneously recorded TC neurons displayed a tonic hyperpolarization associated with repetitive IPSPs, closely time related with cortical cell bursts. The inhibition of TC cells was presumably mediated by GABAergic RE thalamic neurons. Indeed, simultaneously recorded RE and TC neurons during the cortical SW paroxysm showed that cortical and RE cell excitation was accompanied by corresponding IPSPs in TC cells. We emphasize the progressive development from sleep patterns to some forms of epileptic-like activities. We propose that the inhibitory processes found in a significant number of TC cells during cortical SW seizures may contribute to the loss of consciousness, due to obliteration of synaptic transmission through the thalamus.

Animals↗

PubMed1994

Modeling the control of reticular thalamic oscillations by neuromodulators.

Compartmental models of thalamic reticular (RE) neurons were investigated based on current-clamp and voltage-clamp data. Spontaneous oscillations in the model arise from the interaction between inhibitory synaptic currents and the rebound burst of RE cells. These oscillations critically depend on the level of the resting membrane potential. A network of RE neurons can be switched between silent and sustained oscillatory behavior by modulating a leak potassium current through neuromodulatory synapses. These results suggest that neuromodulators, such as noradrenaline, serotonin and glutamate, can exert a decisive control over the oscillatory activity of systems of RE cells. The model may explain why the isolated RE nucleus oscillates spontaneously in vivo but not in vitro.

Electrophysiology↗

PubMed1994

Cortical and thalamic cellular correlates of electroencephalographic burst-suppression.

This experimental study on anesthetized cats used intracellular recordings of cortical, thalamocortical and reticular thalamic neurons (n = 54), as well as multi-site extracellular recordings (n = 36), to investigate the cellular correlates of EEG burst-suppression patterns, defined as alternating wave bursts and periods of electrical silence. Burst-suppression was elicited by the administration of the same or other anesthetic agents upon the background of an already synchronized EEG activity. About 95% of cortical cells entered burst-suppression, in close time-relation with EEG activity, displaying sequences of phasic depolarizing events associated with bursts of EEG waves and an electrical silence of the neuronal membrane during flat EEG epochs. The membrane potential (Vm) hyperpolarized by approximately 10 mV prior to any EEG change and the slow rhythms reflecting deep stages of anesthesia progressively disorganized with transition to burst-suppression. During flat EEG epochs, the apparent input resistance (tested through short hyperpolarizing current pulses) decreased (range 12-60%) and neuronal responsiveness to orthodromic volleys (tested by thalamic and cortical evoked excitatory postsynaptic potentials) was dramatically reduced. It is proposed that the decreased input resistance is mainly due to an increase in K+ conductances. At variance with cortical neurons, only 60-70% of thalamic cells ceased firing before overt EEG burst-suppression and were completely silent during flat periods of EEG activity. The remaining 30-40% of thalamic cells discharged rhythmic (1-4 Hz) spike bursts during periods of EEG silence. This rhythm, within the frequency range of delta waves, is generated in thalamic cells by the interplay between two of their intrinsic currents at critical levels of Vm hyperpolarization. However, with the deepening of burst-suppression, when silent EEG periods became longer than 30 sec, thalamic cells also ceased firing. The assumption that full-blown burst-suppression is achieved through virtually complete disconnection in brain circuits implicated in the genesis of the EEG is corroborated by the revival of normal cellular and EEG activities after volleys setting into action thalamic and cortical networks.

Animals↗

PubMed1994

Synchronized sleep oscillations and their paroxysmal developments.

The state of resting sleep is associated with a series of oscillations generated in cortical and thalamic networks. A newly discovered rhythm groups the spindle and delta sleep oscillations within slowly recurring (< 1 Hz) sequences. Multi-site, extra- and intracellular recordings provide evidence for synchronization of various classes of cell in the neocortex and thalamus during sleep oscillations that might reach paroxysmal levels similar to epileptic states. Sleep oscillations and the underlying synchronizing processes are disrupted during transition to brain arousal.

Animals↗

PubMed1994

A model of spindle rhythmicity in the isolated thalamic reticular nucleus.

1. The oscillatory properties of the isolated reticular (RE) thalamus were modeled with the use of compartmental models of RE cells. Hodgkin-Huxley type kinetic models of ionic channels were derived from voltage- and current-clamp data from RE cells. Interactions between interconnected RE cells were simulated with the use of a kinetic model of gamma-aminobutyric acid (GABA) inhibitory synapses. 2. The intrinsic bursting properties of RE cells in the model were due to the presence of a low-threshold Ca2+ current and two Ca(2+)-activated currents. The properties of these model RE cells were compared with RE neurons recorded intracellularly in vivo in cats. 3. Model RE cells densely interconnected with GABAA synapses produced synchronous oscillations at a frequency close to that of spindles (7-14 Hz). Networks of RE neurons organized in a two-dimensional array with only proximal connectivity also exhibited synchronized oscillations in the spindle range. In addition, the proximally connected network showed periods of high and low synchronicity, giving rise to waxing and waning oscillations in the population of RE cells. 4. The spatiotemporal behavior of the network was investigated during waxing and waning oscillations. The waxing and waning emerged as an alternation between periods of desynchronized and synchronized activity, corresponding to periods of irregular and coherent spatial activity. During synchronized periods, the network displayed propagating coherent waves of synchronous activity that had a tendency to form spirals. 5. Networks of model RE neurons fully connected through GABAB synapses exhibited perfectly synchronous oscillations at lower frequencies (0.5-1 Hz), but two-dimensional networks with proximal GABAB connectivity failed to synchronize. 6. These simulations demonstrate that networks of model neurons that include the main intrinsic currents found in RE cells can generate waxing and waning oscillatory activity similar to the spindle rhythmicity observed in the isolated RE nucleus in vivo. The model reveals the interplay between the intrinsic rhythmic properties of RE cells and the fast synaptic interactions in organizing synchronized rhythmicity.

Afferent Pathways↗